Serum biomarkers for the early diagnosis of TIA: The MIND-TIA study protocol

L Servaas Dolmans, Frans H Rutten, Marie-Louise El Bartelink, Gerdien Seppenwoolde, Sanne van Delft, L Jaap Kappelle, Arno W Hoes, L Servaas Dolmans, Frans H Rutten, Marie-Louise El Bartelink, Gerdien Seppenwoolde, Sanne van Delft, L Jaap Kappelle, Arno W Hoes

Abstract

Background: A Transient Ischaemic Attack (TIA) bears a high risk of a subsequent ischaemic stroke. Adequate diagnosis of a TIA should be followed immediately by the start of appropriate preventive therapy, including antiplatelets. The diagnosis of a TIA based on symptoms and signs only is notoriously difficult and biomarkers of brain ischaemia might improve the recognition, and target management and prognosis of TIA patients. Our aim is to quantify the added diagnostic value of serum biomarkers of brain ischaemia in patients suspected of TIA.

Study design: a cross-sectional diagnostic accuracy study with an additional six month follow-up period.

Study population: 350 patients suspected of TIA in the primary care setting. Patients suspected of a TIA will be recruited by at least 200 general practitioners (GPs) in the catchment area of seven TIA outpatient clinics willing to participate in the study. In all patients a blood sample will be drawn as soon as possible after the patient has contacted the GP, but at least within 72 h after onset of symptoms. Participants will be referred by the GP to the regional TIA outpatient clinic for additional investigations, including brain imaging. The 'definite' diagnosis (reference standard) will be made by a panel consisting of three experienced neurologists who will use all available diagnostic information and the clinical information obtained during the outpatient clinic assessment, and a six month follow-up period. The diagnostic accuracy, and value in addition to signs and symptoms of candidate serum biomarkers will be assessed in terms of discrimination with C statistics, and calibration with plots. We aim to include 350 suspected cases, with 250 patients with indeed definite TIA (or minor stroke) according to the panel.

Discussion: We hope to find novel biomarkers that will enable a rapid and accurate diagnosis of TIA. This would largely improve the management and prognosis of such patients.

Trial registration: ClinicalTrials.gov Identifier NCT01954329.

References

    1. Nichols M, Townsend N, Luengo-Fernandez R, Leal J, Gray A, Scarborough P, et al. European Heart Network. Brussels, Sophia Antipolis: European Society of Cardiology; 2012.
    1. Easton JD, Saver JL, Albers GW, Alberts MJ, Chaturvedi S, Feldmann E, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. Stroke. 2009;40:2276–2293. doi: 10.1161/STROKEAHA.108.192218.
    1. Giles MF, Rothwell PM. Risk of stroke early after transient ischaemic attack: a systematic review and meta-analysis. Lancet Neurol. 2007;6:1063–1072. doi: 10.1016/S1474-4422(07)70274-0.
    1. Wu CM, McLaughlin K, Lorenzetti DL, Hill MD, Manns BJ, Ghali WA. Early risk of stroke after transient ischemic attack: a systematic review and meta-analysis. Arch Intern Med. 2007;167:2417–2422. doi: 10.1001/archinte.167.22.2417.
    1. Rothwell PM, Giles MF, Chandratheva A, Marquardt L, Geraghty O, Redgrave JN, et al. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet. 2007;370:1432–1442. doi: 10.1016/S0140-6736(07)61448-2.
    1. Kappelle LJ. A transient ischaemic attack (TIA) is an emergency. Ned Tijdschr Geneeskd. 2007;151:2761–2763.
    1. Luengo-Fernandez R, Gray AM, Rothwell PM. Effect of urgent treatment for transient ischaemic attack and minor stroke on disability and hospital costs (EXPRESS study): a prospective population-based sequential comparison. Lancet Neurol. 2009;8:235–243. doi: 10.1016/S1474-4422(09)70019-5.
    1. Chalela JA, Kidwell CS, Nentwich LM, Luby M, Butman JA, Demchuk M, et al. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison. Lancet. 2007;369:293–298. doi: 10.1016/S0140-6736(07)60151-2.
    1. Amarenco P, Labreuche J, Lavallee PC. Patients with transient ischemic attack with ABCD2 < 4 can have similar 90-day stroke risk as patients with transient ischemic attack with ABCD2 >/=4. Stroke. 2012;43:863–865. doi: 10.1161/STROKEAHA.111.636506.
    1. Amort M, Fluri F, Schafer J, Weisskopf F, Katan M, Burow A, et al. Transient ischemic attack versus transient ischemic attack mimics: frequency, clinical characteristics and outcome. Cerebrovasc Dis. 2011;32:57–64. doi: 10.1159/000327034.
    1. Fonseca AC, Canhao P. Diagnostic difficulties in the classification of transient neurological attacks. Eur J Neurol. 2011;18:644–648. doi: 10.1111/j.1468-1331.2010.03241.x.
    1. Jensen MB, Chacon MR, Sattin JA, Aleu A, Lyden PD. The promise and potential pitfalls of serum biomarkers for ischemic stroke and transient ischemic attack. Neurologist. 2008;14:243–246. doi: 10.1097/NRL.0b013e31815a9945.
    1. Kernagis DN, Laskowitz DT. Evolving role of biomarkers in acute cerebrovascular disease. Ann Neurol. 2012;71:289–303. doi: 10.1002/ana.22553.
    1. Maas MB, Furie KL. Molecular biomarkers in stroke diagnosis and prognosis. Biomark Med. 2009;3:363–383. doi: 10.2217/bmm.09.30.
    1. Harrell FE, Jr, Lee KL, Califf RM, Pryor DB, Rosati RA. Regression modelling strategies for improved prognostic prediction. Stat Med. 1984;3:143–152. doi: 10.1002/sim.4780030207.
    1. Lavellee PC, Mesequer E, Abboud H, Cabrejo L, Olivot JM, Simon O, et al. A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects. Lancet Neurol. 2007;6:953–960. doi: 10.1016/S1474-4422(07)70248-X.
    1. Castle J, Mlynash M, Lee K, Caulfield AF, Wolford C, Kemp S, et al. Agreement regarding diagnosis of transient ischemic attack fairly low among stroke-trained neurologists. Stroke. 2010;41:1367–1370. doi: 10.1161/STROKEAHA.109.577650.
    1. Moons KG, Grobbee DE. When should we remain blind and when should our eyes remain open in diagnostic studies? J Clin Epidemiol. 2002;55:633–636. doi: 10.1016/S0895-4356(02)00408-0.
    1. Reitsma JB, Rutjes AW, Khan KS, Coomarasamy A, Bossuyt PM. A review of solutions for diagnostic accuracy studies with an imperfect or missing reference standard. J Clin Epidemiol. 2009;62:797–806. doi: 10.1016/j.jclinepi.2009.02.005.
    1. Wunderlich MT, Hanhoff T, Goertler M, Spener F, Glatz J, Wallesch CW, et al. Release of brain-type and heart-type fatty acid-binding proteins in serum after acute ischaemic stroke. J Neurol. 2005;252:718–724. doi: 10.1007/s00415-005-0725-z.
    1. Allard L, Burkhard PR, Lescuyer P, Burgess JA, Walter N, Hochstrasser DF, et al. PARK7 and nucleoside diphosphate kinase A as plasma markers for the early diagnosis of stroke. Clin Chem. 2005;51:2043–2051. doi: 10.1373/clinchem.2005.053942.
    1. Allard L, Turck N, Burkhard PR, Walter N, Rosell A, Gex-Fabry M, et al. Ubiquitin fusion degradation protein 1 as a blood marker for the early diagnosis of ischemic stroke. Biomark Insights. 2007;2:155–164.
    1. Dambinova SA, Bettermann K, Glynn T, Tews M, Olson D, Weissman DJ, et al. Diagnostic potential of the NMDA receptor peptide assay for acute ischemic stroke. PLoS One. 2012;7:e42362. doi: 10.1371/journal.pone.0042362.
    1. Weissman JD, Khunteev GA, Heath R, Dambinova SA. NR2 antibodies: risk assessment of transient ischemic attack (TIA)/stroke in patients with history of isolated and multiple cerebrovascular events. J Neurol Sci. 2011;300:97–102. doi: 10.1016/j.jns.2010.09.023.

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